1. Field of the Invention
The peptides and peptide derivatives herein referred to possess valuable psychopharmacological properties. In particular, they inhibit the extinction of the conditioned flight response, as a result of which they are eminently suitable for the treatment of certain mental disorders in which stimulation of brain function is desirable, such as for senility or other old-age infirmites.
2. Description of the Prior Art
From Eur. J. Pharmacol. 2, 14 (1967) it is known, that certain peptide fragments of the natural adrenocorticotrophic hormones (ACTH) retard the extinction of the conditioned flight response. Specifically, the peptide consisting of the aminoacid sequence 4-10 of ACTH proved to be the smallest peptide fragment active in this respect.
In addition to the psychopharmacological properties noted, the peptide with the amino-acid sequence 4-10 ACTH also possesses slight MSH activity, as is usual with this type of ACTH-fragments. Although the effect of a low dosage of a peptide with MSH activity is still not fully known, a search has nevertheless been made for peptides with at least the same psychopharmacological activity but with no, or much reduced, MSH activity.
In the U.S. Pat. No. 3,853,836 it is revealed that the amino-acid sequence 4-10 ACTH is not essential for psychopharmacological activity, and that this activity is attributable to a much shorter peptide, namely 4-6 ATCH. It furthermore appears that the N-terminal amino-acid L-Met may, without loss of activity, be replaced by D-Met, L- or D-Met(.fwdarw.C), L- or D-Met(.fwdarw.O.sub.2), desamino-Met, desamino-Met(.fwdarw.O) or desamino-Met(.fwdarw.O.sub.2), or by the group ##STR2## in which B represents a branched or straight chain alkylene group with 1-6 carbon atoms.
In the U.S. Pat. No. 3,856,770 it is furthermore reported that replacement of the C-terminal peptide residue --L--Trp--Gly--OH in the original 4- 10 ACTH peptide by one of the groups --L--Phe--OH, L-Phe-Gly-OH, a phenylalkylamino group or a (3-indolyl)alkyl-amino group results in an increase of the psychopharmacological activity.
In the U.S. Pat. No. 3,842,064 it is furthermore reported that a considerable increase of the psychopharmacological activity is obtained by replacing L-arginine in the original 4-10 ACTH peptide, or in one of the modified peptides described in the above-noted patent specifications, by D-lysine.
In this latter paptent specification, the most active peptides are described, namely those peptides conforming to the general formula: EQU A--L--Glu--L--His--L--Phe--D--Lys--L--Phe--(Gly)--OH,
where A has the meaning noted above. These peptides prove to possess an activity which is approximately 1000x stronger than rhat of the original 4-10 ACTH.